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Mar 2024
The microvascular-macrovascular interplay: the next target?
Jan 2024
Targeting residual cardiovascular risk: what’s in the pipeline?
Sep 2023
Remnant cholesterol – evolving evidence
Jul 2023
Call to action on residual stroke risk
Apr 2023
Residual risk in 2023: where to?
Dec 2022
Lipid-related residual risk: lessons from PROMINENT?
Sep 2022
Residual cardiovascular risk: is apolipoprotein B the preferred marker?
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Residual vascular risk in chronic kidney disease: new options on the horizon
Feb 2022
Looking back at 2021 – what made the news?
Nov 2021
New ACC guidance addresses unmet clinical needs for high-risk patients with mild to moderate hypertriglyceridemia
Sep 2021
Residual vascular risk: What matters?
Aug 2021
Understanding vein graft failure: a role for PPARalpha in pathobiology
May 2021
Residual cardiovascular risk: how to identify?
Apr 2021
Metabolic syndrome and COVID-19
Mar 2021
Elevated triglyceride: linking ASCVD and dementia
Feb 2021
Does SPPARMα offer new opportunities in metabolic syndrome and NAFLD?
Jan 2021
Omega-3 fatty acids for residual cardiovascular risk: more questions than answers
Oct 2020
Targeting triglycerides: Novel agents expand the field
Jul 2020
Why multidrug approaches are needed in NASH: insights with pemafibrate
Jun 2020
Triglyceride-rich remnant lipoproteins: a new therapeutic target in aortic valve stenosis?
Mar 2020
Lowering triglycerides or low-density lipoprotein cholesterol: which provides greater clinical benefit?
Feb 2020
The omega-3 fatty acid conundrum
Dec 2019
Focus on stroke: more input to address residual cardiovascular risk
Jul 2019
International Expert Consensus on Selective Peroxisome Proliferator-Activated Receptor Alpha Modulator (SPPARMα): New opportunities for targeting modifiable residual cardiovascular risk
Nov 2018
Residual cardiovascular risk: triglyceride metabolism and genetics provide a key
Jul 2018
The clinical gap for managing residual cardiovascular risk: will new approaches make the difference?
Apr 2018
Residual cardiovascular risk: refocus on a multifactorial approach
Feb 2018
Optimizing treatment benefit: the tenet of personalized medicine
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Addressing residual cardiovascular risk – back to basics?
Dec 2017
Residual risk of heart failure: how to address this global epidemic?
Oct 2017
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Targeting residual cardiovascular risk: lipids and beyond…
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Why we need to re-focus on Latin America.
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Residual cardiovascular risk in the Middle East: a perfect storm in the making
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A global call to action on residual cardiovascular risk
Dec 2016
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New study links elevated triglycerides with plaque progression
Aug 2016
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SPPARM?: a concept becomes clinical reality
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Remnant cholesterol back in the news
May 2016
Back to the future: triglycerides revisited
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Unravelling the heritability of triglycerides and coronary risk
Mar 2016
Will residual cardiovascular risk meet its nemesis in 2016?
Feb 2016
Tackling residual cardiovascular risk: a case for targeting postprandial triglycerides?
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Looking back at 2015: lipid highlights
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Legacy effects in cardiovascular prevention
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Residual cardiovascular risk: it’s not just lipids!
Oct 2015
Addressing residual vascular risk: beyond pharmacotherapy
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Back to basics: triglyceride-rich lipoproteins, remnants and residual vascular risk
Jul 2015
Beyond the PCSK9 decade: what's next?
Jun 2015
Targeting triglycerides: what lies on the horizon for novel therapies?
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Do we need new lipid biomarkers for residual cardiovascular risk?
Apr 2015
The Residual Risk Debate Hots Up: Lowering LDL-C or lowering remnant cholesterol?
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Call for action on stroke
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Triglycerides: the tide has turned
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Post IMPROVE-IT: Where to now for residual risk?
Dec 2014
R3i publishes new Call to Action paper: Residual Microvascular Risk in Type 2 Diabetes in 2014: Is it Time for a Re-Think?
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Non-HDL-C and residual cardiovascular risk: the Lp(a) perspective
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REALIST Micro, atherogenic dyslipidaemia and residual microvascular risk
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Looking back at 2013: what have we learned about residual vascular risk?
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Renewing the R3i call to action: Now more than ever we need to target and treat residual cardiovascular risk
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Time for a re-think on guidelines to reduce residual microvascular risk in diabetes?
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Addressing the residual burden of CVD in renal impairment: do PPARa agonists provide an answer?
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Re-evaluating options for residual risk post-HPS2-THRIVE : are SPPARMs the answer?
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Call to action: re-emphasising the importance of targeting residual vascular risk
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Sep 2011
After SPARCL: Targeting cardio-cerebrovascular metabolic risk and thrombosis to reduce residual risk of stroke
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Challenging the conventional wisdom: Lessons from the FIELD study on diabetic nephropathy
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ACCORD Eye Study: a milestone in residual microvascular risk reduction for patients with type 2 diabetes
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Lipids and residual risk of coronary heart disease in statin-treated patients
Mar 2010
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Dec 2009
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Fasting versus nonfasting triglycerides: Importance of triglyceride-regulating genetic polymorphisms to residual cardiovascular risk
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Reducing residual vascular risk: modifiable and non modifiable residual vascular risk factors
Jan 2009
Micro- and macrovascular residual risk: one of the most challenging health problems of the moment
Nov 2008
Treated dyslipidemic patients remain at high residual risk of vascular events

R3i Editorial

15 June 2012
Time to prioritise atherogenic dyslipidaemia to reduce residual microvascular risk?
Prof. JC Fruchart, Prof. J. Davignon, Prof. M Hermans
Board of the R3i Trustees
 
Prof. JC Fruchart, Prof. J. Davignon, Prof. M Hermans Atherogenic dyslipidaemia, the combination of low plasma levels of high-density lipoprotein (HDL) cholesterol and elevated triglycerides, is an important contributor to residual vascular risk. The recent European Atherosclerosis Society Consensus Panel highlighted atherogenic dyslipidaemia as a key driver of cardiovascular risk, especially in individuals with diabetes and/or metabolic disease.(1) Indeed, both low HDL cholesterol and elevated triglycerides are considered risk factors for cardiovascular disease in the latest European guidelines for management of dyslipidaemia.(2)

Evidence also links atherogenic dyslipidaemia with residual microvascular risk in people with diabetes. Observational data have implicated elevated triglycerides or low HDL cholesterol and the development and progression of diabetic retinopathy, nephropathy and neuropathy.(3-6) Data from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) and Action to Control Cardiovascular Risk in Diabetes (ACCORD) studies in type 2 diabetes patients provide further support. Treatment with fenofibrate, which targets atherogenic dyslipidaemia, positively impacted the progression of diabetic retinopathy and albuminuria, as well as reducing lower limb amputations (especially those arising from microangiopathy).(7-12)

This new report from Zoppini et al (2012)(13) provides further support for the importance of targeting atherogenic dyslipidaemia to reduce microvascular complications in people with type 2 diabetes. Their findings were based on a large prospective cohort, followed over about 5 years. The study clearly highlighted the ratio of triglycerides to HDL cholesterol as an important predictor of the risk of microvascular complications, in particular diabetic nephropathy, beyond conventional risk factors such as glycaemic and blood pressure control.

It is also highly relevant that the prognostic significance of an elevated triglyceride-HDL cholesterol ratio was more pronounced in individuals with well controlled plasma levels of low-density lipoprotein (LDL) cholesterol levels. Previous research has already highlighted the high cardiovascular risk in these patients. In the case-control REALIST Macrovascular Study, the presence of both elevated triglycerides (=190 mg/dL or 2.1 mmol/L) and low HDL cholesterol (<30 mg/dL or 0.78 mmol/L), increased coronary risk 10-fold irrespective of LDL-cholesterol control.(14)

As the number of people with type 2 diabetes escalates, particularly in emerging regions such as Asia and the Middle East, with adoption of Westernised lifestyles, and those with diabetes are living longer, due to advances in management and therapy, the burden of diabetes, especially due to microvascular complications has escalated. The cost implications are enormous, given that the presence of diabetes complications more than doubles the cost of care.(15) Taking action now to limit the development of both micro- and macrovascular diabetes complications, not only makes good clinical sense, but also good economic sense.

These new data, added to other studies, provide renewed emphasis on atherogenic dyslipidaemia as an important modifiable contributor to both macrovascular and microvascular risk in patients with type 2 diabetes at LDL cholesterol goal. On this basis, we propose that interventions targeted to atherogenic dyslipidaemia should be a priority, in addition to current standards of care, to reduce the high residual risk of vascular complications that persists in patients with type 2 diabetes.

References

1. Chapman MJ, Ginsberg HN, Amarenco P et al. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management. Eur Heart J 2011;32:1345-61.
2. Reiner Z, Catapano AL, De Backer G et al. ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J 2011;32:1769-818.
3. Lim LS, Wong TY. Lipids and diabetic retinopathy. Expert Opin Biol Ther 2012;12:93-105.
4. Retnakaran R, Cull CA, Thorne KI et al. Risk factors for renal dysfunction in type 2 diabetes: U.K. Prospective Diabetes Study 74. Diabetes 2006;55:1832-9.
5. Tesfaye S, Chaturvedi N, Eaton SE et al. Vascular risk factors and diabetic neuropathy. N Engl J Med 2005;352:341-50.
6. Kempler P, Tesfaye S, Chaturvedi N et al. Autonomic neuropathy is associated with increased cardiovascular risk factors: the EURODIAB IDDM Complications Study. Diabet Med 2002;19:900-9.
7. Keech AC, Mitchell P, Summanen PA et al. Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial. Lancet 2007;370:1687-97.
8. Ting RD, Keech AC, Drury PL et al. Benefits and safety of long-term fenofibrate therapy in people with type 2 diabetes and renal impairment: the FIELD Study. Diabetes Care 2012;35:218-25.
9. Davis TM, Ting R, Best JD et al. Effects of fenofibrate on renal function in patients with type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study. Diabetologia 2011;54:280-90.
10. Rajamani K, Colman PG, Li LP et al. Effect of fenofibrate on amputation events in people with type 2 diabetes mellitus (FIELD study): a prespecified analysis of a randomised controlled trial. Lancet 2009;373:1780-8.
11. Chew EY, Ambrosius WT, Davis MD et al. Effects of medical therapies on retinopathy progression in type 2 diabetes. N Engl J Med 2010;363:233-44.
12. Mychaleckyj JC, Craven T, Nayak U et al. Reversibility of fenofibrate therapy-induced renal function impairment in ACCORD type 2 diabetic participants. Diabetes Care 2012;35:1008-14.
13. Zoppini G, Negri C, Stoico V, Casati S, Pichiri I, Bonora E. Triglyceride-high-density lipoprotein cholesterol is associated with microvascular complications in type 2 diabetes mellitus. Metabolism 2012;61:22-9.
14. Carey VJ, Bishop L, Laranjo N et al. Contribution of high plasma triglycerides and low high-density lipoprotein cholesterol to residual risk of coronary heart disease after establishment of low-density lipoprotein cholesterol control. Am J Cardiol 2010;106:757-63.
15. Pelletier EM, Shim B, Ben-Joseph R, Caro JJ. Economic outcomes associated with microvascular complications of type 2 diabetes mellitus: results from a US claims data analysis. PharmacoEconomics 2009;27:479-90.
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